Heteroaryl Kinase Inhibitors

Abstract

The present invention provides compounds of Formula (I): and pharmaceutically acceptable salts thereof. Also provided is a method of using a compound of Formula I for treating a disease or condition mediated by a CDK inhibitor.

1 . A compound of Formula I 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein: 
         R 1  is selected from —(CH 2 ) 0-2 -heteroaryl, —(CH 2 ) 0-2 -aryl, C 1-8  alkyl, C 3-8  branched alkyl, C 3-8  cycloalkyl, and a 4 to 8 membered heterocycloalkyl group, wherein said groups are each independently optionally substituted; 
         R 2  is selected from hydrogen, C 1-4  alkoxy, C 1-4  haloalkyl, C 1-4 -alkyl, and halogen; 
         A 1  is N; 
         A 4  is CR 6 ; 
         R 4  is selected from hydrogen, halogen, 5 to 7 membered heterocyclyl-R 14 , and A 6 -L-R 9 ; 
         R 5  is selected from hydrogen, C 1-4  alkyl, C 1-4  haloalkyl, hydroxyl, CN, —O—C 1-4  alkyl, —O—C 1-4  haloalkyl, C 3-4  cycloalkyl, C 3-4  cyclo haloalkyl, and halogen; 
         R 6  is selected from hydrogen, C 1-4  alkyl, C 1-4  haloalkyl, CN, —O—C 1-4  alkyl, C 3-4  cycloalkyl, C 3-4  cyclo haloalkyl, —O—C 1-4  haloalkyl, and halogen; 
         R 7  is selected from hydrogen, C 1-4  alkyl, C 1-4  haloalkyl, O—C 1-3  alkyl, and halogen; 
         A 6  is selected from O, SO 2 , and NR 8 ; 
         L is selected from C 0-3 -alkylene, —CHD-, —CD 2 -, C 3-6  cycloalkyl, C 3-6  cyclo haloalkyl, C 4-7 -heterocycloalkyl, C 3-8  branched alkylene, C 3-8  branched haloalkylene; 
         R 8  is selected from hydrogen, C 1-4  alkyl, and C 3-8  branched-alkyl, and —C 3-8  branched haloalkyl; 
         R 9  is selected from hydrogen, C 1-6  alkyl, C 3-8  cycloalkyl, C 3-8  branched alkyl, —(CH 2 ) 0-2  heteroaryl, (CH 2 ) 0-2 -4 to 8 member heterocycloalkyl, and (CH 2 ) 0-2 -aryl, wherein said groups are optionally substituted; and 
         R 14  is selected from hydrogen, phenyl, halogen, hydroxy, C 1-4 -alkyl, C 3-6 -branched alkyl, C 1-4 -haloalkyl, CF 3 , ═O, and O—C 1-4 -alkyl. 
       
     
     
         2 . A compound of  claim 1 , wherein:
 R 1  is selected from —(CH 2 ) 0-2 -heteroaryl, —(CH 2 ) 0-2 -aryl, wherein said groups are each independently optionally substituted with one to three substituents selected from —NH 2 , —F, —Cl, —OH, —C 1-4  alkyl, —C 1-4  haloalkyl, —C 3-6  branched alkyl, C 3-6  branched haloalkyl, —C 3-7  cyclo alkyl, —C 3-7  cyclo haloalkyl, —(CH 2 ) 1-3 —O—C 1-2  alkyl, —(CH 2 ) 1-3 —O—C 1-2  haloalkyl, —(CH 2 ) 0-2 —O—(CH 2 ) 2-3 —O—C 1-2  alkyl, —(CH 2 ) 0-2 —O—(CH 2 ) 2-3 —O—C 1-2  haloalkyl, —O—C 1-4  alkyl, —O—C 1-4  haloalkyl, —O—C 3-6  branched alkyl, —O—C 3-6  branched haloalkyl, —O—C 3-7  cyclo alkyl, —O—C 3-7  cyclo haloalkyl, —O—(CH 2 ) 1-2 —C 3-6  cycloalkyl-R 14 , —O—(CH 2 ) 1-2 —C 4-6  heterocycloalkyl-R 14 , —NH—C 1-4  alkyl, —NH—C 2-4  haloalkyl, —NH—C 3-8  branched alkyl, —NH—C 3-8  branched haloalkyl, —NH—C 3-7  cyclo alkyl, —NH—C 3-7  cyclo haloalkyl, —NH—C(O)—C 1-4  alkyl, —NH—C(O)—C 1-4  haloalkyl, —NH—C(O)—C 3-8  branched alkyl, —NH—C(O)—C 3-8  branched haloalkyl, —NH—C(O)—C 3-7  cyclo alkyl, —NH—C(O)—C 3-7  cyclo haloalkyl, —NH—C(O)—CH 2 —O—C 1-4  alkyl, —NH—C(O)—CH 2 —O—C 1-4  haloalkyl, —NH—C(O)—O—C 1-4  alkyl, —NH—C(O)O—C 2-4  haloalkyl, —NH—C(O)—O—C 3-8  branched alkyl, —NH—C(O)O—C 3-8  branched haloalkyl, —NH—C(O)—O—C 3-7  cyclo alkyl, —NH—C(O)—O—C 3-7  cyclo haloalkyl, —NH—SO 2 —C 1-4  alkyl, —NH—SO 2 —C 1-4  haloalkyl, —NH—SO 2 —C 3-8  branched alkyl, —NH—SO 2 —C 3-8  branched haloalkyl, —NH—SO 2 —C 3-5  cycloalkyl, —NH—SO 2 —C 3-5  cyclo haloalkyl, —C(O)—O—C 1-4  alkyl, —C(O)—O—C 2-4  halo-alky, —C(O)—O—C 3-6  branched alkyl, —C(O)O—C 3-6  branched haloalkyl, —C(O)—O—C 3-7  cyclo alkyl, —NH—C(O)—O—C 3-7  cyclo haloalkyl, —C(O)—C 1-4  alkyl, —C(O)C 2-4  haloalkyl, —C(O)—C 3-8  branched alkyl, —C(O)—C 3-8  branched haloalkyl, —C(O)—C 3-7  cyclo alkyl, —NH—C(O)—O—C 3-7  cyclo haloalkyl, —C(O)—CH 2 —O—C 1-4  alkyl, —C(O)—CH 2 —O—C 1-4  haloalkyl, —SO 2 —C 1-4  alkyl, —SO 2 —C 1-4  haloalkyl, —SO 2 —C 3-8  branched alkyl, —SO 2 —C 3-8  branched haloalkyl, —SO 2 —C 3-5  cycloalkyl, and —SO 2 —C 3-5  cyclo haloalkyl, —C(O)—NR 15 R 16 , and —SO 2 —NR 15 R 16 , and further wherein, any two said substituents along with the atoms to which they are attached can form a ring;   R 2  is selected from hydrogen, C 1-4  alkoxy, C 1-4  haloalkyl, C 1-4 -alkyl, and halogen;   A 1  is N;   A 4  is CR 6 ;   R 4  is selected from hydrogen, halogen, 5 to 7 membered heterocyclyl-R 14 , and A 6 -L-R 9 ;   R 5  is selected from hydrogen, C 1-4  alkyl, C 1-4  haloalkyl, CN, —O—C 1-4  alkyl, —O—C 1-4  haloalkyl, C 3-4  cycloalkyl, C 3-4  cyclo haloalkyl, and halogen;   R 6  is selected from hydrogen, C 1-4  alkyl, C 1-4  haloalkyl, CN, —O—C 1-4  alkyl, C 3-4  cycloalkyl, C 3-4  cyclo haloalkyl, —O—C 1-4  haloalkyl, and halogen;   R 7  is selected from hydrogen, C 1-4  alkyl, C 1-4  haloalkyl, O—C 1-3  alkyl, and halogen;   A 6  is O, SO 2 , or NR 8 ;   L is selected from C 0-3 -alkylene, —CHD-, —CD 2 -, C 3-6  cycloalkyl, C 3-6  cyclo haloalkyl, C 4-7 -heterocycloalkyl, and C 3-8  branched alkylene;   R 8  is selected from hydrogen, C 1-4  alkyl, and C 3-8  branched-alkyl, and —C 3-8  branched haloalkyl;   R 9  is selected from hydrogen, C 1-6  alkyl, C 3-8  cycloalkyl, C 3-8  branched alkyl, —(CH 2 ) 0-2  heteroaryl, (CH 2 ) 0-2 -4 to 8 member heterocycloalkyl, and (CH 2 ) 0-2 -aryl, wherein said groups are optionally substituted;   R 14  is selected from hydrogen, phenyl, halogen, hydroxy, C 1-4 -alkyl, C 3-6 -branched alkyl, C 1-4 -haloalkyl, CF 3 , ═O, and O—C 1-4 -alkyl; and   R 15  and R 16  are independently selected from hydrogen, hydroxyl, alkyl, branched alkyl, haloalkyl, branched haloalkyl, alkoxy, cycloalkyl and heterocycloalkyl; and alternatively, R 15  and R 16  along with the nitrogen atom to which they are attached to can be taken together to form an optionally substituted four to six membered heteroaromatic, or non-aromatic heterocyclic ring.   
     
     
         3 . A compound of  claim 1 , wherein:
 R 1  is selected from —(CH 2 ) 0-2 -heteroaryl, and —(CH 2 ) 0-2 -aryl, wherein said groups are each independently optionally substituted with one to three substituents selected from the group consisting of —NH 2 , F, Cl, —OH, —C 1-4  alkyl, —NH—C 1-4  alkyl, —C 1-4  haloalkyl, —C 3-6  branched alkyl, —(CH 2 ) 1-3 —O—C 1-2  alkyl, —NH—C(O)—CH 2 —O—C 1-4  alkyl, —NH—C(O)—C 1-4  alkyl, —NH—C(O)—C 3-8  branched alkyl, —O—C 3-6  branched alkyl, —NH—C(O)O—C 1-4  alkyl, —NH—SO 2 —C 1-4  alkyl, —NH—SO 2 —C 3-8  branched alkyl, —NH—SO 2 —C 3-5  cycloalkyl, (CH 2 ) 0-2 —(CH 2 ) 2-3 —O—C 1-2  alkyl, —O—C 1-4  alkyl, —C(O)O—C 3-6  branched alkyl, —C(O)C 1-4  alkyl, —C(O)—O—C 1-4  alkyl, —C(O)—C 3-8  branched alkyl, —C(O)—CH 2 —O—C 1-4  alkyl, —SO 2 —C 1-4  alkyl, —SO 2 —C 3-8  branched alkyl, —O—(CH 2 ) 1-2 —C 3-6  cycloalkyl-R 14 , —O—(CH 2 ) 1-2 —C 4-6  heterocycloalkyl-R 14 , —SO 2 —NR 15 R 16 , and —SO 2 —C 3-5  cycloalkyl;   R 2  is selected from hydrogen, and halogen;   A 1  is N;   A 4  is CR 6 ;   R 4  is selected from piperidinyl, morpholinyl, pyrrolidinyl, and A 6 -L-R 9 ; wherein each said piperidinyl, morpholinyl, pyrrolidinyl group is substituted with R 14 ;   R 5  is selected from hydrogen, Cl, F, and CF 3 ;   R 6  is hydrogen;   R 7  is selected from hydrogen, F, and Cl;   A 6  is NR 8 ;   L is selected from C 0-3 -alkylene, —CD 2 -, and C 3-8  branched alkylene;   R 8  is selected from hydrogen, and C 1-4  alkyl;   R 9  is selected from C 1-3  alkyl, C 3-7  cycloalkyl, C 4-6  branched alkyl, —(CH 2 ) 1-3 —O—C 1-4  alkyl, —(CH 2 )-pyridyl, (CH 2 )-4 to 8 member heterocycloalkyl, (CH 2 )-4 to 8 member heterocycloalkyl, and (CH 2 )-phenyl, wherein said groups are optionally substituted with one to three substituents selected from hydrogen, halogen, C 1-4  alkyl, C 1-4  haloalkyl, —OH, CN, ═O, C(O)—CH 3 , —O—C 1-3  alkyl, —O—C 1-3  haloalkyl, —O—(CH 2 ) 2-3 —O—C 1-2  alkyl, —C(O)—C 1-4  alkyl, and —NH—C(O)—C 1-4  alkyl;   R 14  is selected from phenyl, halogen, hydroxyl, C 1-2 -alkyl, CF 3 , and hydrogen; and   R 15  and R 16  are independently selected from hydrogen, hydroxyl, alkyl, branched alkyl, haloalkyl, branched haloalkyl, alkoxy, cycloalkyl and heterocycloalkyl; and alternatively, R 15  and R 16  along with the nitrogen atom to which they are attached to can be taken together to form an optionally substituted four to six membered heteroaromatic, or non-aromatic heterocyclic ring.   
     
     
         4 . A compound of  claim 1 , wherein:
 R 1  is selected from C 1-8  alkyl, C 3-8  cycloalkyl, C 3-8  branched alkyl, and a 4 to 8 membered heterocycloalkyl group, wherein said groups are each independently optionally substituted with one to three substituents selected from —NH 2 , —F, —OH, ═O, —C 1-4  alkyl, —C 1-4  haloalkyl, —C 3-6  branched alkyl, C 3-6  branched haloalkyl, —C 3-7  cyclo alkyl, —C 3-7  cyclo haloalkyl, —(CH 2 ) 1-3 —O—C 1-2  alkyl, —(CH 2 ) 1-3 —O—C 1-2  haloalkyl, —(CH 2 ) 0-2 —O—(CH 2 ) 2-3 —O—C 1-2  alkyl, —(CH 2 ) 0-2 —O—(CH 2 ) 2-3 —O—C 1-2  haloalkyl, —O—C 1-4  alkyl, —O—C 1-4  haloalkyl, —O—C 3-6  branched alkyl, —O—C 3-6  branched haloalkyl, —O—C 3-7  cyclo alkyl, —O—C 3-7  cyclo haloalkyl, —O—(CH 2 ) 1-2 —C 3-6  cycloalkyl-R 14 , —O—(CH 2 ) 1-2 —C 4-6  heterocycloalkyl-R 14 , —NH—C 1-4  alkyl, —NH—C 2-4  haloalkyl, —NH—C 3-8  branched alkyl, —NH—C 3-8  branched haloalkyl, —NH—C 3-7  cyclo alkyl, —NH—C 3-7  cyclo haloalkyl, —NH—C(O)—C 1-4  alkyl, —NH—C(O)—C 1-4  haloalkyl, —NH—C(O)—C 3-8  branched alkyl, —NH—C(O)—C 3-8  branched haloalkyl, —NH—C(O)—C 3-7  cyclo alkyl, —NH—C(O)—C 3-7  cyclo haloalkyl, —NH—C(O)—CH 2 —O—C 1-4  alkyl, —NH—C(O)—CH 2 —O—C 1-4  haloalkyl, —NH—C(O)—O—C 1-4  alkyl, —NH—C(O)O—C 2-4  haloalkyl, —NH—C(O)—O—C 3-8  branched alkyl, —NH—C(O)O—C 3-8  branched haloalkyl, —NH—C(O)—O—C 3-7  cyclo alkyl, —NH—C(O)—O—C 3-7  cyclo haloalkyl, —NH—SO 2 —C 1-4  alkyl, —NH—SO 2 —C 1-4  haloalkyl, —NH—SO 2 —C 3-8  branched alkyl, —NH—SO 2 —C 3-8  branched haloalkyl, —NH—SO 2 —C 3-5  cycloalkyl, —NH—SO 2 —C 3-5  halo-cycloalkyl, —C(O)—O—C 1-4  alkyl, —C(O)—O—C 2-4  halo-alky, —C(O)—O—C 3-6  branched alkyl, —C(O)O—C 3-6  branched haloalkyl, —C(O)—O—C 3-7  cyclo alkyl, —NH—C(O)—O—C 3-7  cyclo haloalkyl, —C(O)—C 1-4  alkyl, —C(O)C 2-4  haloalkyl, —C(O)—C 3-8  branched alkyl, —C(O)—C 3-8  branched haloalkyl, —C(O)—C 3-7  cyclo alkyl, —NH—C(O)—O—C 3-7  cyclo haloalkyl, —C(O)—CH 2 —O—C 1-4  alkyl, —C(O)—CH 2 —O—C 1-4  haloalkyl, —SO 2 —C 1-4  alkyl, —SO 2 —C 1-4  haloalkyl, —SO 2 —C 3-8  branched alkyl, —SO 2 —C 3-8  branched haloalkyl, —SO 2 —C 3-5  cycloalkyl, and —SO 2 —C 3-5  cyclo haloalkyl; —C(O)—NR 15 R 16 , and —SO 2 —NR 15 R 16 , and further wherein, any two said substituents along with the atoms to which they are attached can form a ring;   R 2  is selected from hydrogen, C 1-4  alkoxy, C 1-4  haloalkyl, C 1-4 -alkyl, and halogen;   A 1  is N;   A 4  is CR 6 ;   R 4  is selected from hydrogen, halogen, 5 to 7 membered heterocyclyl-R 14 , and A 6 -L-R 9 ;   R 5  is selected from hydrogen, C 1-4  alkyl, C 1-4  haloalkyl, CN, —O—C 1-4  alkyl, —O—C 1-4  haloalkyl, C 3-4  cycloalkyl, C 3-4  cyclo haloalkyl, and halogen;   R 6  is selected from hydrogen, C 1-4  alkyl, C 1-4  haloalkyl, CN, —O—C 1-4  alkyl, C 3-4  cycloalkyl, C 3-4  cyclo haloalkyl, and halogen;   R 7  is selected from hydrogen, C 1-4  alkyl, C 1-4  haloalkyl, O—C 1-3  alkyl, and halogen;   A 6  is selected from O, SO 2 , and NR 8 ;   L is selected from C 0-3 -alkylene, —CHD-, —CD 2 -, C 3-6  cycloalkyl, C 3-6  cyclo haloalkyl, C 4-7 -heterocycloalkyl, C 3-8  branched alkylene, C 3-8  branched haloalkylene;   R 8  is selected from hydrogen, C 1-4  alkyl, and C 3-8  branched-alkyl, and —C 3-8  branched haloalkyl;   R 9  is selected from hydrogen, C 1-6  alkyl, C 3-8  cycloalkyl, C 3-8  branched alkyl, —(CH 2 ) 0-2  heteroaryl, (CH 2 ) 0-2 -4 to 8 member heterocycloalkyl, and (CH 2 ) 0-2 -aryl, wherein said groups are optionally substituted;   R 14  is selected from hydrogen, phenyl, halogen, hydroxy, C 1-4 -alkyl, C 3-6 -branched alkyl, C 1-4 -haloalkyl, CF 3 , ═O, and O—C 1-4 -alkyl; and   R 15  and R 16  are independently selected from hydrogen, hydroxyl, alkyl, branched alkyl, haloalkyl, branched haloalkyl, alkoxy, cycloalkyl and heterocycloalkyl; and alternatively, R 15  and R 16  along with the nitrogen atom to which they are attached to can be taken together to form an optionally substituted four to six membered heteroaromatic, or non-aromatic heterocyclic ring.   
     
     
         5 . A compound of  claim 1 , wherein:
 R 1  is selected from C 1-8  alkyl, C 3-8  branched alkyl, C 3-8  cycloalkyl, and a 4 to 8 membered heterocycloalkyl group, wherein said groups are each independently optionally substituted with one to three substituents selected from the group consisting of —NH 2 , F, —OH, ═O, —C 1-4  alkyl, —NH—C 1-4  alkyl, —C 1-4  haloalkyl, —C 3-6  branched alkyl, —(CH 2 ) 1-3 —O—C 1-2  alkyl, —NH—C(O)—CH 2 —O—C 1-4  alkyl, —NH—C(O)—C 1-4  alkyl, —NH—C(O)—C 3-8  branched alkyl, —O—C 3-6  branched alkyl, —NH—C(O)—O—C 1-4  alkyl, —NH—SO 2 —C 1-4  alkyl, —NH—SO 2 —C 3-8  branched alkyl, —NH—SO 2 —C 3-5  cycloalkyl, (CH 2 ) 0-2 —O—(CH 2 ) 2-3 —O—C 1-2  alkyl, —O—C 1-4  alkyl, —C(O)O—C 3-6  branched alkyl, —C(O)C 1-4  alkyl, —C(O)—O—C 1-4  alkyl, —C(O)—C 3-8  branched alkyl, —C(O)—CH 2 —O—C 1-4  alkyl, —SO 2 —C 1-4  alkyl, —SO 2 —C 3-8  branched alkyl, and —SO 2 —C 3-5  cycloalkyl;   R 2  is selected from hydrogen, and halogen;   A 1  is N;   A 4  is CR 6 ;   R 4  is selected from piperidinyl, morpholinyl, pyrrolidinyl, and A 6 -L-R 9 ; wherein each said piperidinyl, morpholinyl, pyrrolidinyl group is substituted with R 14 ;   R 5  is selected from hydrogen, Cl, F, and CF 3 ;   R 6  is hydrogen;   R 7  is selected from hydrogen, F, and Cl;   A 6  is NR 8 ;   L is selected from C 0-3 -alkylene, —CD 2 -, and C 3-8  branched alkylene;   R 8  is selected from hydrogen, and C 1-4  alkyl;   R 9  is selected from C 1-3  alkyl, C 3-7  cycloalkyl, C 4-6  branched alkyl, —(CH 2 ) 1-3 —O—C 1-4  alkyl, —(CH 2 )-pyridyl, (CH 2 )-4 to 8 member heterocycloalkyl, (CH 2 )-4 to 8 member heterocycloalkyl, and (CH 2 )-phenyl, wherein said groups are optionally substituted with one to three substituents selected from hydrogen, halogen, C 1-4  alkyl, C 1-4  haloalkyl, —OH, CN, ═O, C(O)—CH 3 , —O—C 1-3  alkyl, —O—C 1-3  haloalkyl, —O—(CH 2 ) 2-3 —O—C 1-2  alkyl, —C(O)—C 1-4  alkyl, and —NH—C(O)—C 1-4  alkyl; and   R 14  is selected from phenyl, halogen, hydroxy, C 1-2 -alkyl, and hydrogen.   
     
     
         6 . A compound of  claim 1 , wherein:
 R 1  is selected from piperidinyl, morpholinyl, 1-methylpiperidinyl, tetrahydro-pyran, pyrrolidinyl, tetrahydro-furan, azetidine, pyrrolidin-2-one, azepane, and 1,4-oxazepane, wherein said R 1  groups are each independently optionally substituted with one to three substituents selected from F, OH, NH 2 , CO-methyl, —NH-methyl, ethyl, fluoro-ethyl, trifluoro-ethyl, (CH 2 ) 2 -methoxy, SO 2 —CH 3 , COO—CH 3 , SO 2 -ethyl, SO 2 -cyclopropyl, methyl, SO 2 —CH—(CH 3 ) 2 , NH—SO 2 —CH 3 , NH—SO 2 —C 2 H 5 , ═O, CF 3 , (CH 2 )-methoxy, methoxy, NH—SO 2 —CH—(CH 3 ) 2 , —(CH 2 )—O—(CH 2 ) 2 -methoxy, —O—CH—(CH 3 ) 2 ;   R 2  is selected from Cl, and F;   A 1  is N;   A 4  is CR 6 ;   R 4  is A 6 -L-R 9 ;   R 5  is selected from Cl, F, and hydrogen;   R 6  is H;   R 7  is selected from hydrogen, F, and Cl;   A 6  is NR 8 ;   L is selected from C 0-3 -alkylene, —CD 2 -, and C 3-8  branched alkylene;   R 8  is selected from hydrogen, and methyl; and   R 9  is selected from C 1-3  alkyl, C 4-6  branched alkyl, —(CH 2 ) 1-3 —O—C 1-4  alkyl, —(CH 2 )-pyridyl, benzyl, CD 2 -tetrahydro-pyran, tetrahydro-pyran, tetrahydro-thiopyran 1,1-dioxide, piperidinyl, pyrrolidine-2-one, dioxane, cyclopropyl, tetrahydrofuran, cyclohexyl, and cycloheptyl, wherein said groups are optionally substituted with one to three substituents each independently selected from F, OCHF 2 , CO-methyl, OH, methyl, methoxy, CN, ethyl, and NH—CO-methyl.   
     
     
         7 . A compound of  claim 1 , wherein:
 R 1  is selected from piperidinyl, morpholinyl, pyrrolidinyl, azepane, and 1,4-oxazepane, wherein said R 1  groups are each independently optionally substituted with one to three substituents selected from F, methyl, CF 3 , ethyl, fluoro-ethyl, trifluoro-ethyl, —(CH 2 ) 2 -methoxy, —(CH 2 )-methoxy, methoxy, ═O, —(CH 2 )—O—(CH 2 ) 2 -methoxy, and —O—CH—(CH 3 ) 2 ;   R 2  is Cl;   R 4  is A 6 -L-R 9 ;   R 5  is selected from Cl, F, and hydrogen;   R 6  is H;   R 7  is selected from Cl, F, and hydrogen;   A 6  is NR 8 ;   L is selected from —CH 2 —, and —CD 2 -;   R 8  is selected from hydrogen, and methyl; and   R 9  is selected from pyridyl, benzyl, tetrahydro-pyran, dioxane, and tetrahydrofuran, wherein said groups are optionally substituted with one to three substituents each independently selected from F, OH, methyl, ethyl, methoxy, and CN.   
     
     
         8 . A compound according to any one of  claims 1  to  7 , or pharmaceutically acceptable salt thereof, for use in a method of treating a disease or condition mediated by CDK9. 
     
     
         9 . The use of a compound according to any one of  claims 1  to  7 , or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment of a disease or condition mediated by CDK9. 
     
     
         10 . A method of treatment of a disease or condition mediated by CDK9 comprising administration to a subject in need thereof a therapeutically effective amount of a compound according to any one of  claims 1  to  7 , or a pharmaceutically acceptable salt thereof 
     
     
         11 . A pharmaceutical composition comprising a compound according to any one of  claims 1  to  7 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient. 
     
     
         12 . A compound of  claim 1  selected from:
 ((1R,3S)-3-{3,5′-Dichloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-ylcarbamoyl}-cyclopentyl)-carbamic acid methyl ester; 
 (1S,3R)-3-(Propane-2-sulfonylamino)-cyclopentanecarboxylic acid {3,5′-dichloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (S)-3-{5′-Chloro-6-[(1′,1′-dioxo-hexahydro-1-thiopyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-ylcarbamoyl}-piperidine-1-carboxylic acid methyl ester; 
 (S)-3-{3,5′-Dichloro-6-[(2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-ylcarbamoyl}-piperidine-1-carboxylic acid methyl ester; 
 ((1S,3R)-3-{3,5′-Dichloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-ylcarbamoyl}-cyclopentyl)-carbamic acid methyl ester; 
 (S)-1-Methanesulfonyl-piperidine-3-carboxylic acid {3,5′-dichloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (S)-1-(Propane-2-sulfonyl)-piperidine-3-carboxylic acid {3,5′-dichloro-6-[((S)-2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (1R,3S)-3-Methanesulfonylamino-cyclopentanecarboxylic acid {3,5′-dichloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (1S,3R)-3-Ethanesulfonylamino-cyclopentanecarboxylic acid {3,5′-dichloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (S)-1-Ethanesulfonyl-piperidine-3-carboxylic acid {3,5′-dichloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (S)-3-{3,5′-Dichloro-6-[((R)-2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-ylcarbamoyl}-piperidine-1-carboxylic acid methyl ester; 
 (S)-1-Methanesulfonyl-piperidine-3-carboxylic acid {5′-chloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (S)-1-(Propane-2-sulfonyl)-piperidine-3-carboxylic acid {3,5′-dichloro-6-[(2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (S)-1-(Propane-2-sulfonyl)-piperidine-3-carboxylic acid {3,5′-dichloro-6-[((R)-2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (1S,3R)-3-Methanesulfonylamino-cyclopentanecarboxylic acid {3,5′-dichloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (S)-1-Ethanesulfonyl-piperidine-3-carboxylic acid {5′-chloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; and 
 (S)-1-(Propane-2-sulfonyl)-piperidine-3-carboxylic acid {3,5′-dichloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide. 
 
     
     
         13 . A compound of  claim 1  selected from:
 (R)-Piperidine-3-carboxylic acid {5′-chloro-6-[((2R,6S)-2,6-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Pyrrolidine-3-carboxylic acid {5′-chloro-6-[((S)-2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Pyrrolidine-3-carboxylic acid {5′-chloro-6-[((2R,6S)-2,6-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Piperidine-3-carboxylic acid {5′-chloro-6-[((R)-2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Piperidine-3-carboxylic acid {5′-chloro-6-[((S)-6,6-dimethyl-[1,4]dioxan-2-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Piperidine-3-carboxylic acid {5′-chloro-6-[((R)-2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-5-fluoro-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Pyrrolidine-3-carboxylic acid {5′-chloro-6-[((R)-2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Piperidine-3-carboxylic acid {5′-chloro-6-[((S)-2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Piperidine-3-carboxylic acid {5′-chloro-6-[((S)-2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-5-fluoro-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Piperidine-3-carboxylic acid {5′-chloro-6-[((S)-6,6-dimethyl-[1,4]dioxan-2-ylmethyl)-amino]-5-fluoro-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Piperidine-3-carboxylic acid {5′-chloro-6-[((R)-6,6-dimethyl-[1,4]dioxan-2-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; and 
 (R)-Piperidine-3-carboxylic acid {5′-chloro-6-[((R)-5,5-dimethyl-[1,4]dioxan-2-ylmethyl)-amino]-5-fluoro-[2,4′]bipyridinyl-2′-yl}-amide. 
 
     
     
         14 . A compound of  claim 1  selected from:
 (R)-Piperidine-3-carboxylic acid {3,5′-dichloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Piperidine-3-carboxylic acid {5′-chloro-5-fluoro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Piperidine-3-carboxylic acid {5′-chloro-3-fluoro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Piperidine-3-carboxylic acid {5′-chloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Pyrrolidine-3-carboxylic acid {5′-chloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Pyrrolidine-3-carboxylic acid {3,5′-dichloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Pyrrolidine-3-carboxylic acid {5′-chloro-5-fluoro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Piperidine-3-carboxylic acid {5,5′-dichloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Piperidine-3-carboxylic acid {3,5,5′-trichloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; and 
 (R)-Piperidine-3-carboxylic acid {3-chloro-5′-fluoro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide. 
 
     
     
         15 . A compound of  claim 1  selected from:
 (3R,6R)-6-Methyl-piperidine-3-carboxylic acid {5′-chloro-6-[((R)-2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (3R,5S)-5-Trifluoromethyl-piperidine-3-carboxylic acid {5′-chloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (3R,6R)-6-Ethyl-piperidine-3-carboxylic acid {5′-chloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (3R,5S)-5-Methyl-piperidine-3-carboxylic acid {5′-chloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (3R,6R)-6-Methyl-piperidine-3-carboxylic acid {5′-chloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (3R,6R)-6-Methyl-piperidine-3-carboxylic acid {5′-chloro-6-[((S)-2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (3R,6R)-6-Methyl-piperidine-3-carboxylic acid {5′-chloro-5-fluoro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (3R,6S)-6-Methyl-piperidine-3-carboxylic acid {5′-chloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; and 
 (3R,6R)-6-Ethyl-piperidine-3-carboxylic acid {5′-chloro-5-fluoro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide. 
 
     
     
         16 . A compound of  claim 1  selected from:
 (R)-Piperidine-3-carboxylic acid {5′-chloro-6-[(4-cyano-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Piperidine-3-carboxylic acid {5′-chloro-6-[(4-methyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Piperidine-3-carboxylic acid {5′-chloro-6-[(4-fluoro-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Piperidine-3-carboxylic acid {5′-chloro-5-fluoro-6-[(4-methyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Piperidine-3-carboxylic acid {3,5′-dichloro-6-[(4-methoxy-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Piperidine-3-carboxylic acid {5′-chloro-5-fluoro-6-[(4-methoxy-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; and 
 (R)-Piperidine-3-carboxylic acid {5′-chloro-6-[(4-ethyl-tetrahydro-pyran-4-ylmethyl)-amino]-5-fluoro-[2,4′]bipyridinyl-2′-yl}-amide. 
 
     
     
         17 . A compound of  claim 1  selected from:
 (1S,3R)-3-Amino-cyclopentanecarboxylic acid {5′-chloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Piperidine-3-carboxylic acid [5′-chloro-6-(3-fluoro-benzylamino)-[2,4′]bipyridinyl-2′-yl]-amide; 
 6-Oxo-piperidine-3-carboxylic acid {5′-chloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (1S,3R)-3-Amino-cyclopentanecarboxylic acid {3,5′-dichloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (1R,3R)-3-Amino-cyclopentanecarboxylic acid {5′-chloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (1R,3S)-3-Amino-cyclopentanecarboxylic acid {3,5′-dichloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Piperidine-3-carboxylic acid [5′-chloro-6-(3,5-difluoro-benzylamino)-[2,4′]bipyridinyl-2′-yl]-amide; and 
 (1R,3S)-3-Amino-cyclopentanecarboxylic acid {5′-chloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide. 
 
     
     
         18 . A compound of  claim 1  selected from:
 (3R,5S)-5-Methoxymethyl-pyrrolidine-3-carboxylic acid {5′-chloro-5-fluoro-6-[(4-methoxy-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (3R,5S)-5-Methoxymethyl-pyrrolidine-3-carboxylic acid {5′-chloro-6-[(4-methyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (3S,4R)-4-Methoxy-pyrrolidine-3-carboxylic acid {5′-chloro-6-[(2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (3R,5S)-5-Methoxymethyl-pyrrolidine-3-carboxylic acid {3,5′-dichloro-6-[(2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (3S,4R)-4-Methoxy-pyrrolidine-3-carboxylic acid {3,5′-dichloro-5-fluoro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (3S,4R)-4-Methoxy-pyrrolidine-3-carboxylic acid {5′-chloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (3R,5S)-5-Methoxymethyl-pyrrolidine-3-carboxylic acid {3,5′-dichloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (3S,4R)-4-Methoxy-pyrrolidine-3-carboxylic acid {3,5′-dichloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (3S,4R)-4-Methoxy-pyrrolidine-3-carboxylic acid {5′-chloro-5-fluoro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; and 
 (3S,4R)-4-Methoxy-pyrrolidine-3-carboxylic acid {5′-chloro-6-[((2R,6S)-2,6-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide. 
 
     
     
         19 . A compound of  claim 1  selected from:
 (R)-Morpholine-2-carboxylic acid {5′-chloro-5-fluoro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (S)-[1,4]Oxazepane-6-carboxylic acid {3,5′-dichloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Morpholine-2-carboxylic acid {5′-chloro-3-fluoro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Morpholine-2-carboxylic acid {3,5′-dichloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Morpholine-2-carboxylic acid {5′-chloro-6-[((R)-2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Morpholine-2-carboxylic acid {3,5′-dichloro-6-[((R)-2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Morpholine-2-carboxylic acid {3,5′-dichloro-6-[((S)-2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Morpholine-2-carboxylic acid {5′-chloro-6-[(tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide; and 
 (R)-Morpholine-2-carboxylic acid {5′-chloro-6-[((S)-2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-amino]-[2,4′]bipyridinyl-2′-yl}-amide. 
 
     
     
         20 . A compound according to any one of  claims 12  to  19 , or pharmaceutically acceptable salt thereof, for use in a method of treating a disease or condition mediated by CDK9. 
     
     
         21 . The use of a compound according to any one of  claims 12  to  19 , or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment of a disease or condition mediated by CDK9. 
     
     
         22 . A method of treatment of a disease or condition mediated by CDK9 comprising administration to a subject in need thereof a therapeutically effective amount of a compound according to any one of  claims 12  to  19 , or a pharmaceutically acceptable salt thereof. 
     
     
         23 . A pharmaceutical composition comprising a compound according to any one of  claims 12  to  19 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient. 
     
     
         24 . A compound of Formula II 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein: 
         R 1  is selected from —(CH 2 ) 0-2 -heteroaryl, —(CH 2 ) 0-2 -aryl, C 1-8  alkyl, C 3-8  branched alkyl, C 3-8  cycloalkyl, and a 4 to 8 membered heterocycloalkyl group, wherein said groups are each independently optionally substituted; 
         R 2  is selected from hydrogen, C 1-4  alkoxy, C 1-4  haloalkyl, C 1-4 -alkyl, and halogen; 
         A 1  is CR 3 ; 
         A 4  is N; 
         R 3  is selected from hydrogen, C 1-4  alkyl, C 1-4  haloalkyl, CN, —O—C 1-4  alkyl, C 3-4  cycloalkyl, C 3-4  cyclo haloalkyl, —O—C 1-4  haloalkyl, and halogen; 
         R 4  is selected from hydrogen, halogen, 5 to 7 membered heterocyclyl-R 14 , and A 6 -L-R 9 ; 
         R 5  is selected from hydrogen, C 1-4  alkyl, C 1-4  haloalkyl, hydroxyl, CN, —O—C 1-4  alkyl, —O—C 1-4  haloalkyl, C 3-4  cycloalkyl, C 3-4  cyclo haloalkyl, and halogen; 
         R 7  is selected from hydrogen, C 1-4  alkyl, C 1-4  haloalkyl, O—C 1-3  alkyl, and halogen; 
         A 6  is selected from O, SO 2 , and NR 8 ; 
         L is selected from C 0-3 -alkylene, —CHD-, —CD 2 -, C 3-6  cycloalkyl, C 3-6  cyclo haloalkyl, C 4-7 -heterocycloalkyl, C 3-8  branched alkylene, C 3-8  branched haloalkylene; 
         R 8  is selected from hydrogen, C 1-4  alkyl, and C 3-8  branched-alkyl, and —C 3-8  branched haloalkyl; 
         R 9  is selected from hydrogen, C 1-6  alkyl, C 3-8  cycloalkyl, C 3-8  branched alkyl, —(CH 2 ) 0-2  heteroaryl, (CH 2 ) 0-2 -4 to 8 member heterocycloalkyl, and (CH 2 ) 0-2 -aryl, wherein said groups are optionally substituted; and 
         R 14  is selected from hydrogen, phenyl, halogen, hydroxy, C 1-4 -alkyl, H, C 3-6 -branched alkyl, C 1-4 -haloalkyl, CF 3 , ═O, and O—C 1-4 -alkyl. 
       
     
     
         25 . A compound of  claim 24 , wherein:
 R 1  is selected from —(CH 2 ) 0-2 -heteroaryl, —(CH 2 ) 0-2 -aryl, wherein said groups are each independently optionally substituted with one to three substituents selected from —NH 2 , —F, —Cl, —OH, —C 1-4  alkyl, —C 1-4  haloalkyl, —C 3-6  branched alkyl, C 3-6  branched haloalkyl, —C 3-7  cyclo alkyl, —C 3-7  cyclo haloalkyl, —(CH 2 ) 1-3 —O—C 1-2  alkyl, —(CH 2 ) 1-3 —O—C 1-2  haloalkyl, —(CH 2 ) 0-2 —O—(CH 2 ) 2-3 —O—C 1-2  alkyl, —(CH 2 ) 0-2 —O—(CH 2 ) 2-3 —O—C 1-2  haloalkyl, —O—C 1-4  alkyl, —O—C 1-4  haloalkyl, —O—C 3-6  branched alkyl, —O—C 3-6  branched haloalkyl, —O—C 3-7  cyclo alkyl, —O—C 3-7  cyclo haloalkyl, —O—(CH 2 ) 1-2 —C 3-6  cycloalkyl-R 14 , —O—(CH 2 ) 1-2 —C 4-6  heterocycloalkyl-R 14 , —NH—C 1-4  alkyl, —NH—C 2-4  haloalkyl, —NH—C 3-8  branched alkyl, —NH—C 3-8  branched haloalkyl, —NH—C 3-7  cyclo alkyl, —NH—C 3-7  cyclo haloalkyl, —NH—C(O)—C 1-4  alkyl, —NH—C(O)—C 1-4  haloalkyl, —NH—C(O)—C 3-8  branched alkyl, —NH—C(O)—C 3-8  branched haloalkyl, —NH—C(O)—C 3-7  cyclo alkyl, —NH—C(O)—C 3-7  cyclo haloalkyl, —NH—C(O)—CH 2 —O—C 1-4  alkyl, —NH—C(O)—CH 2 —O—C 1-4  haloalkyl, —NH—C(O)—O—C 1-4  alkyl, —NH—C(O)O—C 2-4  haloalkyl, —NH—C(O)—O—C 3-8  branched alkyl, —NH—C(O)O—C 3-8  branched haloalkyl, —NH—C(O)—O—C 3-7  cyclo alkyl, —NH—C(O)—O—C 3-7  cyclo haloalkyl, —NH—SO 2 —C 1-4  alkyl, —NH—SO 2 —C 1-4  haloalkyl, —NH—SO 2 —C 3-8  branched alkyl, —NH—SO 2 —C 3-8  branched haloalkyl, —NH—SO 2 —C 3-5  cycloalkyl, —NH—SO 2 —C 3-5  cyclo haloalkyl, —C(O)—O—C 1-4  alkyl, —C(O)—O—C 2-4  halo-alky, —C(O)—O—C 3-6  branched alkyl, —C(O)O—C 3-6  branched haloalkyl, —C(O)—O—C 3-7  cyclo alkyl, —NH—C(O)—O—C 3-7  cyclo haloalkyl, —C(O)—C 1-4  alkyl, —C(O)C 2-4  haloalkyl, —C(O)—C 3-8  branched alkyl, —C(O)—C 3-8  branched haloalkyl, —C(O)—C 3-7  cyclo alkyl, —NH—C(O)—O—C 3-7  cyclo haloalkyl, —C(O)—CH 2 —O—C 1-4  alkyl, —C(O)—CH 2 —O—C 1-4  haloalkyl, —SO 2 —C 1-4  alkyl, —SO 2 —C 1-4  haloalkyl, —SO 2 —C 3-8  branched alkyl, —SO 2 —C 3-8  branched haloalkyl, —SO 2 —C 3-5  cycloalkyl, and —SO 2 —C 3-5  cyclo haloalkyl, —C(O)—NR 15 R 16 , and —SO 2 —NR 15 R 16 , and further wherein, any two said substituents along with the atoms to which they are attached can form a ring;   R 2  is selected from hydrogen, C 1-4  alkoxy, C 1-4  haloalkyl, C 1-4 -alkyl, and halogen;   A 1  is CR 3 ;   A 4  is N;   R 3  is selected from hydrogen, C 1-4  alkyl, C 1-4  haloalkyl, CN, —O—C 1-4  alkyl, C 3-4  cycloalkyl, C 3-4  cyclo haloalkyl, —O—C 1-4  haloalkyl, and halogen;   R 4  is selected from hydrogen, halogen, 5 to 7 membered heterocyclyl-R 14 , or A 6 -L-R 9 ;   R 5  is selected from hydrogen, C 1-4  alkyl, C 1-4  haloalkyl, CN, —O—C 1-4  alkyl, —O—C 1-4  haloalkyl, C 3-4  cycloalkyl, C 3-4  cyclo haloalkyl, and halogen;   R 7  is selected from hydrogen, C 1-4  alkyl, C 1-4  haloalkyl, O—C 1-3  alkyl, and halogen;   A 6  is O, SO 2 , or NR 8 ;   L is selected from C 0-3 -alkylene, —CHD-, —CD 2 -, C 3-6  cycloalkyl, C 3-6  cyclo haloalkyl, C 4-7 -heterocycloalkyl, C 3-8  branched alkylene;   R 8  is selected from hydrogen, C 1-4  alkyl, and C 3-8  branched-alkyl, and —C 3-8  branched haloalkyl;   R 9  is selected from hydrogen, C 1-6  alkyl, C 3-8  cycloalkyl, C 3-8  branched alkyl, —(CH 2 ) 0-2  heteroaryl, (CH 2 ) 0-2 -4 to 8 member heterocycloalkyl, and (CH 2 ) 0-2 -aryl, wherein said groups are optionally substituted;   R 14  is selected from hydrogen, phenyl, halogen, hydroxy, C 1-4 -alkyl, H, C 3-6 -branched alkyl, C 1-4 -haloalkyl, CF 3 , ═O, and O—C 1-4 -alkyl; and   R 15  and R 16  are independently selected from hydrogen, hydroxyl, alkyl, branched alkyl, haloalkyl, branched haloalkyl, alkoxy, cycloalkyl and heterocycloalkyl; and alternatively, R 15  and R 16  along with the nitrogen atom to which they are attached to can be taken together to form an optionally substituted four to six membered heteroaromatic, or non-aromatic heterocyclic ring.   
     
     
         26 . A compound of  claim 24 , wherein:
 R 1  is selected from —(CH 2 ) 0-2 -heteroaryl, and —(CH 2 ) 0-2 -aryl, wherein said groups are each independently optionally substituted with one to three substituents selected from the group consisting of —NH 2 , F, Cl, —OH, —C 1-4  alkyl, —NH—C 1-4  alkyl, —C 1-4  haloalkyl, —C 3-6  branched alkyl, —(CH 2 ) 1-3 —O—C 1-2  alkyl, —NH—C(O)—CH 2 —O—C 1-4  alkyl, —NH—C(O)—C 1-4  alkyl, —NH—C(O)—C 3-8  branched alkyl, —O—C 3-6  branched alkyl, —NH—C(O)O—C 1-4  alkyl, —NH—SO 2 —C 1-4  alkyl, —NH—SO 2 —C 3-8  branched alkyl, —NH—SO 2 —C 3-5  cycloalkyl, (CH 2 ) 0-2 —O—(CH 2 ) 2-3 —O—C 1-2  alkyl, —O—C 1-4  alkyl, —C(O)O—C 3-6  branched alkyl, —C(O)C 1-4  alkyl, —C(O)—O—C 1-4  alkyl, —C(O)—C 3-8  branched alkyl, —C(O)—CH 2 —O—C 1-4  alkyl, —SO 2 —C 1-4  alkyl, —SO 2 —C 3-8  branched alkyl, —O—(CH 2 ) 1-2 —C 3-6  cycloalkyl-R 14 , —O—(CH 2 ) 1-2 —C 4-6  heterocycloalkyl-R 14 , —SO 2 —NR 15 R 16 , and —SO 2 —C 3-5  cycloalkyl;   R 2  is selected from hydrogen, and halogen;   A 1  is CR 3 ;   A 4  is N;   R 3  is hydrogen;   R 4  is selected from piperidinyl, morpholinyl, pyrrolidinyl, and A 6 -L-R 9 ; wherein each said piperidinyl, morpholinyl, pyrrolidinyl group is substituted with R 14 ;   R 5  is selected from hydrogen, Cl, F, and CF 3 ;   R 7  is selected from hydrogen, F, and Cl;   A 6  is NR 8 ;   L is selected from C 0-3 -alkylene, —CD 2 -, and C 3-8  branched alkylene;   R 8  is selected from hydrogen, and C 1-4  alkyl;   R 9  is selected from C 1-3  alkyl, C 3-7  cycloalkyl, C 4-6  branched alkyl, —(CH 2 ) 1-3 —O—C 1-4  alkyl, —(CH 2 )-pyridyl, (CH 2 )-4 to 8 member heterocycloalkyl, (CH 2 )-4 to 8 member heterocycloalkyl, and (CH 2 )-phenyl, wherein said groups are optionally substituted with one to three substituents selected from hydrogen, halogen, C 1-4  alkyl, C 1-4  haloalkyl, —OH, CN, ═O, C(O)—CH 3 , —O—C 1-3  alkyl, —O—C 1-3  haloalkyl, —O—(CH 2 ) 2-3 —O—C 1-2  alkyl, —C(O)—C 1-4  alkyl, and —NH—C(O)—C 1-4  alkyl;   R 14  is selected from phenyl, halogen, hydroxyl, C 1-2 -alkyl, CF 3 , and hydrogen; and   R 15  and R 16  are independently selected from hydrogen, hydroxyl, alkyl, branched alkyl, haloalkyl, branched haloalkyl, alkoxy, cycloalkyl and heterocycloalkyl; and alternatively, R 15  and R 16  along with the nitrogen atom to which they are attached to can be taken together to form an optionally substituted four to six membered heteroaromatic, or non-aromatic heterocyclic ring.   
     
     
         27 . A compound of  claim 24 , wherein:
 R 1  is selected from C 1-8  alkyl, C 3-8  cycloalkyl, C 3-8  branched alkyl, and a 4 to 8 membered heterocycloalkyl group, wherein said groups are each independently optionally substituted with one to three substituents selected from —NH 2 , —F, —OH, ═O, —C 1-4  alkyl, —C 1-4  haloalkyl, —C 3-6  branched alkyl, C 3-6  branched haloalkyl, —C 3-7  cyclo alkyl, —C 3-7  cyclo haloalkyl, —(CH 2 ) 1-3 —O—C 1-2  alkyl, —(CH 2 ) 1-3 —O—C 1-2  haloalkyl, —(CH 2 ) 0-2 —O—(CH 2 ) 2-3 —O—C 1-2  alkyl, —(CH 2 ) 0-2 —O—(CH 2 ) 2-3 —O—C 1-2  haloalkyl, —O—C 1-4  alkyl, —O—C 1-4  haloalkyl, —O—C 3-6  branched alkyl, —O—C 3-6  branched haloalkyl, —O—C 3-7  cyclo alkyl, —O—C 3-7  cyclo haloalkyl, —O—(CH 2 ) 1-2 —C 3-6  cycloalkyl-R 14 , —O—(CH 2 ) 1-2 —C 4-6  heterocycloalkyl-R 14 , —NH—C 1-4  alkyl, —NH—C 2-4  haloalkyl, —NH—C 3-8  branched alkyl, —NH—C 3-8  branched haloalkyl, —NH—C 3-7  cyclo alkyl, —NH—C 3-7  cyclo haloalkyl, —NH—C(O)—C 1-4  alkyl, —NH—C(O)—C 1-4  haloalkyl, —NH—C(O)—C 3-8  branched alkyl, —NH—C(O)—C 3-8  branched haloalkyl, —NH—C(O)—C 3-7  cyclo alkyl, —NH—C(O)—C 3-7  cyclo haloalkyl, —NH—C(O)—CH 2 —O—C 1-4  alkyl, —NH—C(O)—CH 2 —O—C 1-4  haloalkyl, —NH—C(O)—O—C 1-4  alkyl, —NH—C(O)O—C 2-4  haloalkyl, —NH—C(O)—O—C 3-8  branched alkyl, —NH—C(O)O—C 3-8  branched haloalkyl, —NH—C(O)—O—C 3-7  cyclo alkyl, —NH—C(O)—O—C 3-7  cyclo haloalkyl, —NH—SO 2 —C 1-4  alkyl, —NH—SO 2 —C 1-4  haloalkyl, —NH—SO 2 —C 3-8  branched alkyl, —NH—SO 2 —C 3-8  branched haloalkyl, —NH—SO 2 —C 3-5  cycloalkyl, —NH—SO 2 —C 3-5  halo-cycloalkyl, —C(O)—O—C 1-4  alkyl, —C(O)—O—C 2-4  halo-alky, —C(O)—O—C 3-6  branched alkyl, —C(O)O—C 3-6  branched haloalkyl, —C(O)—O—C 3-7  cyclo alkyl, —NH—C(O)—O—C 3-7  cyclo haloalkyl, —C(O)—C 1-4  alkyl, —C(O)C 2-4  haloalkyl, —C(O)—C 3-8  branched alkyl, —C(O)—C 3-8  branched haloalkyl, —C(O)—C 3-7  cyclo alkyl, —NH—C(O)—O—C 3-7  cyclo haloalkyl, —C(O)—CH 2 —O—C 1-4  alkyl, —C(O)—CH 2 —O—C 1-4  haloalkyl, —SO 2 —C 1-4  alkyl, —SO 2 —C 1-4  haloalkyl, —SO 2 —C 3-8  branched alkyl, —SO 2 —C 3-8  branched haloalkyl, —SO 2 —C 3-5  cycloalkyl, and —SO 2 —C 3-5  cyclo haloalkyl; —C(O)—NR 15 R 16 , and —SO 2 —NR 15 R 16 , and further wherein, any two said substituents along with the atoms to which they are attached can form a ring;   R 2  is selected from hydrogen, C 1-4  alkoxy, C 1-4  haloalkyl, C 1-4 -alkyl, and halogen;   A 1  is CR 3 ;   A 4  is N;   R 3  is selected from hydrogen, C 1-4  alkyl, C 1-4  haloalkyl, CN, —O—C 1-4  alkyl, C 3-4  cycloalkyl, C 3-4  cyclo haloalkyl, and halogen;   R 4  is selected from hydrogen, halogen, 5 to 7 membered heterocyclyl-R 14 , and A 6 -L-R 9 ;   R 5  is selected from hydrogen, C 1-4  alkyl, C 1-4  haloalkyl, CN, —O—C 1-4  alkyl, —O—C 1-4  haloalkyl, C 3-4  cycloalkyl, C 3-4  cyclo haloalkyl, and halogen;   R 7  is selected from hydrogen, C 1-4  alkyl, C 1-4  haloalkyl, O—C 1-3  alkyl, and halogen;   A 6  is selected from O, SO 2 , and NR 8 ;   L is selected from C 0-3 -alkylene, —CHD-, —CD 2 -, C 3-6  cycloalkyl, C 3-6  cyclo haloalkyl, C 4-7 -heterocycloalkyl, C 3-8  branched alkylene, C 3-8  branched haloalkylene;   R 8  is selected from hydrogen, C 1-4  alkyl, and C 3-8  branched-alkyl, and —C 3-8  branched haloalkyl;   R 9  is selected from hydrogen, C 1-6  alkyl, C 3-8  cycloalkyl, C 3-8  branched alkyl, —(CH 2 ) 0-2  heteroaryl, (CH 2 ) 0-2 -4 to 8 member heterocycloalkyl, and (CH 2 ) 0-2 -aryl, wherein said groups are optionally substituted;   R 14  is selected from hydrogen, phenyl, halogen, hydroxy, C 1-4 -alkyl, H, C 3-6 -branched alkyl, C 1-4 -haloalkyl, CF 3 , ═O, and O—C 1-4 -alkyl; and   R 15  and R 16  are independently selected from hydrogen, hydroxyl, alkyl, branched alkyl, haloalkyl, branched haloalkyl, alkoxy, cycloalkyl and heterocycloalkyl; and alternatively, R 15  and R 16  along with the nitrogen atom to which they are attached to can be taken together to form an optionally substituted four to six membered heteroaromatic, or non-aromatic heterocyclic ring.   
     
     
         28 . A compound of  claim 24 , wherein:
 R 1  is selected from C 1-8  alkyl, C 3-8  branched alkyl, C 3-8  cycloalkyl, and a 4 to 8 membered heterocycloalkyl group, wherein said groups are each independently optionally substituted with one to three substituents selected from the group consisting of —NH 2 , F, —OH, ═O, —C 1-4  alkyl, —NH—C 1-4  alkyl, —C 1-4  haloalkyl, —C 3-6  branched alkyl, —(CH 2 ) 1-3 —O—C 1-2  alkyl, —NH—C(O)—CH 2 —O—C 1-4  alkyl, —NH—C(O)—C 1-4  alkyl, —NH—C(O)—C 3-8  branched alkyl, —O—C 3-6  branched alkyl, —NH—C(O)—O—C 1-4  alkyl, —NH—SO 2 —C 1-4  alkyl, —NH—SO 2 —C 3-8  branched alkyl, —NH—SO 2 —C 3-5  cycloalkyl, (CH 2 ) 0-2 —O—(CH 2 ) 2-3 —O—C 1-2  alkyl, —O—C 1-4  alkyl, —C(O)O—C 3-6  branched alkyl, —C(O)C 1-4  alkyl, —C(O)—O—C 1-4  alkyl, —C(O)—C 3-8  branched alkyl, —C(O)—CH 2 —O—C 1-4  alkyl, —SO 2 —C 1-4  alkyl, —SO 2 —C 3-8  branched alkyl, and —SO 2 —C 3-5  cycloalkyl;   R 2  is selected from hydrogen, and halogen;   A 1  is CR 3 ;   A 4  is N;   R 3  is hydrogen;   R 4  is selected from piperidinyl, morpholinyl, pyrrolidinyl, and A 6 -L-R 9 ; wherein each said piperidinyl, morpholinyl, pyrrolidinyl group is substituted with R 14 ;   R 5  is selected from hydrogen, Cl, F, and CF 3 ;   R 7  is selected from hydrogen, F, and Cl;   A 6  is NR 8 ;   L is selected from C 0-3 -alkylene, —CD 2 -, and C 3-8  branched alkylene;   R 8  is selected from hydrogen, and C 1-4  alkyl;   R 9  is selected from C 1-3  alkyl, C 3-7  cycloalkyl, C 4-6  branched alkyl, —(CH 2 ) 1-3 —O—C 1-4  alkyl, —(CH 2 )-pyridyl, (CH 2 )-4 to 8 member heterocycloalkyl, (CH 2 )-4 to 8 member heterocycloalkyl, and (CH 2 )-phenyl, wherein said groups are optionally substituted with one to three substituents selected from hydrogen, halogen, C 1-4  alkyl, C 1-4  haloalkyl, —OH, CN, ═O, C(O)—CH 3 , —O—C 1-3  alkyl, —O—C 1-3  haloalkyl, —O—(CH 2 ) 2-3 —O—C 1-2  alkyl, —C(O)—C 1-4  alkyl, and —NH—C(O)—C 1-4  alkyl; and   R 14  is selected from phenyl, halogen, hydroxy, C 1-2 -alkyl, and hydrogen.   
     
     
         29 . A compound of  claim 24 , wherein:
 R 1  is selected from piperidinyl, morpholinyl, 1-methylpiperidinyl, tetrahydro-pyran, pyrrolidinyl, tetrahydro-furan, azetidine, pyrrolidin-2-one, azepane, and 1,4-oxazepane, wherein said R 1  groups are each independently optionally substituted with one to three substituents selected from F, OH, NH 2 , CO-methyl, —NH-methyl, ethyl, fluoro-ethyl, trifluoro-ethyl, (CH 2 ) 2 -methoxy, SO 2 —CH 3 , COO—CH 3 , SO 2 -ethyl, SO 2 -cyclopropyl, methyl, SO 2 —CH—(CH 3 ) 2 , NH—SO 2 —CH 3 , NH—SO 2 —C 2 H 5 , ═O, CF 3 , (CH 2 )-methoxy, methoxy, NH—SO 2 —CH—(CH 3 ) 2 , —(CH 2 )—O—(CH 2 ) 2 -methoxy, —O—CH—(CH 3 ) 2 ;   R 2  is selected from Cl, and F;   A 1  is CR 3 ,   A 4  is N;   R 3  is hydrogen;   R 4  is A 6 -L-R 9 ;   R 5  is selected from Cl, F, and hydrogen;   R 6  is H;   R 7  is selected from hydrogen, F, and Cl;   A 6  is NR 8 ;   L is selected from C 0-3 -alkylene, —CD 2 -, and C 3-8  branched alkylene;   R 8  is selected from hydrogen, and methyl; and   R 9  is selected from C 1-3  alkyl, C 4-6  branched alkyl, —(CH 2 ) 1-3 —O—C 1-4  alkyl, —(CH 2 )-pyridyl, benzyl, CD 2 -tetrahydro-pyran, tetrahydro-pyran, tetrahydro-thiopyran 1,1-dioxide, piperidinyl, pyrrolidine-2-one, dioxane, cyclopropyl, tetrahydrofuran, cyclohexyl, and cycloheptyl, wherein said groups are optionally substituted with one to three substituents each independently selected from F, OCHF 2 , CO-methyl, OH, methyl, methoxy, CN, ethyl, and NH—CO-methyl.   
     
     
         30 . A compound of  claim 24 , wherein:
 R 1  is selected from piperidinyl, morpholinyl, pyrrolidinyl, azepane, and 1,4-oxazepane, wherein said R 1  groups are each independently optionally substituted with one to three substituents selected from F, methyl, CF 3 , ethyl, fluoro-ethyl, trifluoro-ethyl, —(CH 2 ) 2 -methoxy, —(CH 2 )-methoxy, methoxy, ═O, —(CH 2 )—O—(CH 2 ) 2 -methoxy, —O—CH—(CH 3 ) 2 ;   R 2  is Cl;   A 1  is CR 3 ;   A 4  is N;   R 3  is hydrogen;   R 4  is A 6 -L-R 9 ;   R 5  is selected from Cl, F, and hydrogen;   R 6  is H;   R 7  is selected from Cl, F, and hydrogen;   A 6  is NR 8 ;   L is selected from —CH 2 —, —CD 2 -;   R 8  is selected from hydrogen, and methyl; and   R 9  is selected from pyridyl, benzyl, tetrahydro-pyran, dioxane, tetrahydrofuran, wherein said groups are optionally substituted with one to three substituents each independently selected from F, OH, methyl, ethyl, methoxy, CN.   
     
     
         31 . A compound of  claim 24  selected from:
 (R)-Piperidine-3-carboxylic acid {2,5′-dichloro-5-[(tetrahydro-pyran-4-ylmethyl)-amino]-[3,4′]bipyridinyl-2′-yl}-amide; 
 (R)-Piperidine-3-carboxylic acid {6,5′-dichloro-5-[(tetrahydro-pyran-4-ylmethyl)-amino]-[3,4′]bipyridinyl-2′-yl}-amide; and 
 (R)-Piperidine-3-carboxylic acid {5′-chloro-5-[(tetrahydro-pyran-4-ylmethyl)-amino]-[3,4′]bipyridinyl-2′-yl}-amide. 
 
     
     
         32 . A compound according to any one of  claims 30  to  31 , or pharmaceutically acceptable salt thereof, for use in a method of treating a disease or condition mediated by CDK9. 
     
     
         33 . The use of a compound according to any one of  claims 30  to  31 , or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment of a disease or condition mediated by CDK9. 
     
     
         34 . A method of treatment of a disease or condition mediated by CDK9 comprising administration to a subject in need thereof a therapeutically effective amount of a compound according to any one of  claims 30  to  31 , or a pharmaceutically acceptable salt thereof. 
     
     
         35 . A pharmaceutical composition comprising a compound according to any one of  claims 30  to  31 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient.